The investigations outlined in this proposal will examine the hypothesis that sympathetic autonomic neuropathy and vasculopathy develop early in diabetes mellitus and that early insulin treatment will prevent or reverse these abnormalities. Specifically, the goal of this proposal is to: 1) determine the longitudial development of autonomic neuropathy and vasculopathy in experimental diabetes mellitus after induction of diabetes in the juvenile and adult rat; 2) determine the incidence of autonomic neuropathy and vasculopathy in juvenile and adult-onset human diabetes mellitus at specific times after the onset of the diabetes; 3) determine the prevention or reversal of 1 and 2 with insulin treatment. A modified Folkow hindquarter perfusion technique will be used with norepinephrine analysis to make determinations about the rat hindquarter vascular bed in experimental diabetes mellitus. Reflex autonomic tests, norepinephrine analysis and plethysmography plus brachial artery drug injections will be used to assess the forearm vasculature of humans. The importance of the proposed study is twofold. First, the natural history of diabetes mellitus in experimental models and humans can be determined and compared. This will provide an insight into the similarities and contrasts between experimental and human diabetes mellitus. Secondly, the influence of age of diabetic onset on the natural history of diabetes mellitus can be determined by assessing juvenile versus adult-onset diabetes mellitus in each group. This work will contribute substantially to my long term goal: to provide pathophysiologic data from which a logical treatment of juvenile and adult-onset diabetes mellitus can be based. If early insulin treatmetn is found to be more effective than delayed treatment, support for aggressive early detection and treatment of diabetes mellitus will be gained.